Preface

Malaria is a major public health issue in sub-Saharan Africa, affecting communities and healthcare systems. Rural communities' knowledge and practices are crucial for malaria prevention and control efforts. Understanding transmission mechanisms, control measures, and modeling is essential for developing effective intervention strategies. Community perceptions and experiences about malaria prevention interventions, such as insecticide-treated bed nets, influence their acceptability and effectiveness. Addressing treatment-seeking behavior, particularly in vulnerable urban populations, is crucial. In-depth qualitative studies are needed to inform targeted interventions. Integrated malaria prevention approaches, including mosquito control, have shown promising results in reducing malaria incidence. However, challenges like low knowledge among migrant farmers and over-treatment in different transmission dynamics need to be addressed. This book provides a contemporary overview of the most important findings in malaria research during the previous few years. The book has four sections.

Section 1 provides an "Overview of Malaria", including information on malaria transmission, diagnosis, treatment, and prevention. It discusses the global public health concern of malaria, malaria prevalence, transmission mechanisms, treatment, control measures, and how modeling is essential for developing effective intervention strategies.

Section 2, "Malaria Transmission", covers perspectives of One Health, zoonotic malaria, environmental transmission, sentinel site and transmission dynamics, and the emergence of insecticide resistance. Malaria transmission is a complex process influenced by environmental, biological, and socioeconomic factors. Topographic features, meteorological conditions, and vector distribution contribute to the disease's transmission. Human activities, such as agricultural practices, can also affect the transmission of malaria. Local-scale hotspots and seasonal migrant workers can resurgence in certain regions. Understanding the spatio-temporal dynamics of malaria is crucial for targeted control strategies. Integrated vector management strategies are effective in controlling transmission, but strategic planning and operational frameworks are needed. Citizen science can monitor vector dynamics and install long-lasting insecticidal nets to break the chain of transmission. Understanding these factors is essential for developing targeted and effective malaria control interventions.

Section 3, "Malaria Diagnosis", discusses the contemporary breakthroughs in malaria diagnosis advancement and the use of unusual sample types. Malaria diagnosis is crucial for disease management, especially in developing countries. Traditional methods like blood examinations are outdated, but newer techniques like antigen tests and polymerase chain reaction (PCR) are gaining traction due to their higher specificity and sensitivity.

Section 4, "Malaria Treatment", focuses on malaria treatment landscapes, current trends, and future perspectives with particular interest in the combination therapy of quinoline nucleus and artemisinin derivatives for the management of uncomplicated malaria. Malaria treatment has evolved, focusing on developing effective drugs. However, drug-resistant *Plasmodium falciparum* strains pose challenges, necessitating individualized drug choices based on disease severity, form, and agent resistance. Widespread resistance hinders antifolates and aminoquinolines in chemotherapy.

This book is required reading for anyone interested in the current state of malaria control efforts, challenges including drug and insecticide resistance, the high cost of control tools, and efforts to develop new tools and genetic control strategies.

### **Linda Eva Amoah (Ph.D.) and Festus Kojo Acquah (Ph.D.)**

Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana

#### **Kwame Kumi Asare (Ph.D.)**

Biomedical and Clinical Research Centre, University of Cape Coast, Cape Coast, Ghana

## Acknowledgement

First and foremost, we want to thank everyone who assisted in the publication of this book. Typists and photographers were among those who worked on this book, as were proofreaders, editors, and content consultants. We want to thank each chapter contributor personally for taking time out of their busy schedules to write the chapters and revise and update information as needed. All these people's efforts, support, and passion were crucial in developing this book for publication. We apologize in advance for those we may have overlooked.

### Section 1

## Overview of Malaria

#### **Chapter 1**

## Malaria-Transmission-Diagnosis and Treatment

*Marisol Sandoval-De Mora*

#### **Abstract**

Malaria is a potentially fatal infectious disease, considered a serious public health problem in the world, caused by a parasite of the *Plasmodium* genus. It is transmitted by the bite of the infected female *Anopheles* mosquito, also after blood transfusions, organ transplantation, sharing contaminated syringes in parenteral drug users, in hospitals, and during pregnancy by vertical transmission. The possibility of diagnosis should be considered in any patient with fever during the stay or return from an endemic area, applying microscopy examination through thick drop and smear, rapid diagnostic tests (RDTs), and molecular diagnostic tests (PCR). Specific treatment is based on the parasite species identified, drug resistance, severity of symptoms, or presence of mixed infection. Treatment is based on oral or intravenous artemisinin and severe forms may require supportive measures and surveillance in intensive care units. This chapter aims to provide knowledge about the dynamics of malarial infection, with emphasis on transmission, diagnostic methods, *Plasmodium* species, and current treatment regimen.

**Keywords:** fever, microscopy, PCR, RDTs, artemisinin, treatment regimen

#### **1. Introduction**

Malaria is an infectious disease caused by a *Plasmodium* parasite, which is transmitted by the bite of an infected mosquito, of which the main vector is the female of the genus *Anopheles* [1].

The high number of malaria cases in 2021 (241 million) and deaths (627,000) reveal the fragility of medical services. Especially in the African region where 96% of all deaths were due to malaria, and 80% in children under 5 years of age, more efforts are needed to reverse the trends of recent years. Globally, the number of people at risk of acquiring the disease is high and in areas of high transmission, the most affected with the development of severe disease and death are children and pregnant women. In 2019, it ranked 6th among the leading causes of death in low-resource countries [1–3].

Symptoms of the disease may include the classic form of manifestation "fever, sweating and chills" that appear 10–15 days after the mosquito bite; in addition, headache and vomiting, among others, may be associated. To make the diagnosis, microscopic studies of the patient's blood, such as thick and thin blood smear, are required. Rapid diagnostic tests (RDTs) are also available to identify malaria in dispersed rural

areas, with difficult geographical access and without infrastructure for microscopic diagnosis [1, 4].

There are five species of *Plasmodium* responsible for producing the disease in humans, the most frequent being *P. vivax, P. falciparum*, and *P. malariae* and *P. ovale* are rarer. Some primate malarial parasites such as *P. knowlesi, P. cynomolgi*, *and P. simium* can also infect humans and *P. knowlesi* is mentioned as a species that is naturally transmitted to macaques in Southeast Asia and infects humans causing "zoonotic" malaria; cases have been described in Malaysia with hyperparasitemia and severe complications that can lead to death [4, 5].

Of all these, *P. falciparum* infection is the most severe and causes several clinical conditions of organ damage, called complicated malaria; it can be fatal, if not treated in time [4, 6].

Chloroquine was the drug of choice for malaria and is still administered in most countries to treat *P. vivax* infection; however, it is rarely used in cases of *P. falciparum* because there is currently disseminated resistance to it; therefore, Artemisinin-based combination therapies (ACTs) are now recommended as the main treatment for this parasitic species [1].

In this chapter, the special relevance of this disease in the world will be discussed, with the general objective being to present updated knowledge on general aspects of malaria, its transmission mode, diagnostic methods, and recommended treatment.

#### **2. Transmission**

Malaria occurs mainly in tropical regions of sub-Saharan Africa, Asia, Oceania, and Latin America and is transmitted, as previously described, by the bite of the infected female *Anopheles* mosquito. Other forms of transmission are: through blood transfusions, organ transplantation, use of contaminated syringes in intravenous drug users, in hospitals where syringes are reused, and from mother to fetus (called gestational malaria) [4–5].

#### **2.1 High and low transmission areas**

Devastating epidemics can occur when the parasite is introduced into an area where the population has had little contact with it and lacks immunity, or when people living in malaria-free areas move to regions where the disease is endemic and can be triggered by climatic conditions, aggravated by natural phenomena such as floods or massive population movements caused by conflicts [1].

The World Health Organization (WHO) recommends the use of different categories depending on the magnitude of transmission according to the situation of each region, the annual parasite incidence, and prevalence of *P. falciparum and P. falciparum/P. vivax* infection [2]:


Differences in propagation from one area to another may be due to geographic characteristics, parasite species and vector distribution, socio-demographic characteristics, access to antimalarial treatment, and extensive vector control [8].

A serious problem is the presence of asymptomatic people with malaria and its impact on the transmission and prevalence of the disease, which usually goes unnoticed. They are reservoirs and constitute a focus of infection for people without immunity, which should keep control programs alert in order to initiate and maintain a surveillance system for the early diagnosis of these people, active case detection is important to diagnose these patients. In 2010, in Amazonas state, Venezuela, 81% of PCR tests for *Plasmodium spp.* were diagnosed in asymptomatic persons [9].

#### **3. Diagnosis**

Clinical suspicion of malaria is established in any patient with fever during the stay or upon return from an endemic area. Diagnostic tests for this entity are: thick and thin blood smears (gold standard), rapid diagnostic tests (RDTs), and PCR molecular diagnostic tests [4].

Symptoms and signs are nonspecific; suspicion is raised primarily on clinical grounds, based on fever. In endemic areas, any patient with temperature ≥ 37.5°C should be considered for confirmation with a parasitological test; results should preferably be available in less than 2 hours.

Parasitological diagnosis: The two methods routinely used to identify microorganisms are: optical microscopy and immunochromatography, the latter detects specific antigens of the parasite or its enzymes that are genus or species specific.

In almost all cases of symptomatic malaria, thick and thin blood smears performed by a competent microscopist will reveal the presence of malarial parasites [2, 4].

#### **3.1 Diagnosis of malaria**

In patients with suspected malaria and in other risk groups such as those living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS), the absence of a parasitological diagnosis should not delay the initiation of antimalarial treatment, which should be started immediately.

#### **3.2 Optical microscopy**

Microscopic results have not only high sensitivity and specificity for the diagnosis of malaria but also allow quantification of the magnitude of the infection and the parasite species involved. However, the use of this diagnostic resource is costly because it requires the experience and vigilance of the personnel.

Although molecular biology tests are more sensitive, the thick blood smear is still considered the "field standard" against which the sensitivity and specificity of other methods must be compared [10].

Therefore, microscopic examination provides good specificity for the diagnosis of malaria as a febrile illness present. Other important advantages of light microscopy are:


Numerous tests have been done to improve it, but none have proven superior to the classical Giemsa and immersion oil staining method [2, 12].

#### **3.3 Rapid diagnostic test (RDTs)**

There are several tests, which are increasingly useful to complement microscopic findings [13–15].

Rapid diagnostic tests detect by immunochromatography specific *Plasmodium* antigens in the blood of people with malaria. Some tests identify a single species (*P. falciparum)*; others identify one or more of the other parasites that affect humans [16–18].

They are commercially available, in strips, cassettes and cards, and easy to use. They are relatively simple to execute and interpret and do not require electricity or special equipment [16, 19].

Since 2012, the World Health Organization (WHO) has recommended that these tests should be selected according to criteria based on contribution results from the WHO Malaria RDT Product Testing program [2, 20].

Current tests are based on the detection of histidine-rich protein 2 (PfHRP2), which is specific for *P. falciparum,* pan-specific or species-specific *Plasmodium* lactate dehydrogenase (LDH), or pan-specific aldolase [2, 21–23].

They have potential advantages including:


Disadvantages:


#### **3.4 Immunodiagnostic and nucleic acid amplification test methods**

Immunodiagnostic tests directly detect the presence of the parasite by capturing parasite antigens during infection, which can be useful for epidemiological studies but lack sensitivity [26].

Techniques to detect nucleic acids such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification are highly sensitive and useful for detecting mixed infection, particularly when there is a low degree of parasitemia, not detectable by light microscopy or with RDTs. They are recommended for drug resistance and epidemiological studies, but their use is not recommended in malaria-endemic areas for routine diagnosis.

So far, nucleic acid amplification tests do not play a role in the clinical management of malaria or in surveillance systems [2, 27].

It is worth noting that malaria surveillance programs should use conventional methods for diagnosis: thick blood smears and RDTs, and leave molecular tests (PCR) for special situations. At the community level, clinical symptoms suggestive of the disease can be used to initiate treatment when RDTs are not available. While in primary care centers, thick blood smears or RDTs or both should be used to decide on treatment. In secondary or tertiary care, light microscopy is important to confirm the diagnosis, measure parasitemia and control follow-up, and only if there are an excessive number of patients, the use of RDTs is preferred. Some patients negative to microscopy and RDTs may have a low degree of parasitemia and will only be diagnosed by performing PCR, which is a more sensitive method [9, 28]

#### **4. Treatment**

Treatment depends on the *Plasmodium* species, severity of the disease, drug resistance, age of the patient, and pregnancy [2, 4].

#### **4.1 Treatment of uncomplicated** *P. falciparum* **malaria**

Uncomplicated malaria is defined as a patient who presents symptoms and signs of this entity (fever, myalgia, among others) and a positive parasitological examination (microscopy or RDTs) without features of severity and the objectives of treatment are to cure the infection as quickly as possible and prevent the progression to severe disease [2].

#### **4.2 Artemisinin-based combination therapy (ACTs)**

For this clinical form, artemisinin combinations (ACTs) are available, with duration of 3 days and covering two asexual cycles. In relation to the doses, they must be optimal to guarantee rapid clinical and parasitological cure, decrease transmission, and avoid drug resistance [2, 4, 6].

The WHO recommends the following treatment regimens: [2].

#### *4.2.1 Artemether + Lumefantrine*

Dosage of 5–24 mg/kg/bw of artemether and 29–144 mg/kg/bw of lumefantrine; administer twice daily, for 3 days (total of 6 doses), the first 2 doses should be given 8 hours apart.

The formulations currently available are tablets of 20 mg of artemether and 120 mg of lumefantrine and another presentation of 40 mg of artemether and 240 mg of lumefantrine, in fixed doses and in combination formulation.

#### *4.2.2 Artesunate + Amodiaquine*

Dosage of 4 mg/kg/bw artesunate and 10 mg/kg/bw amodiaquine, once daily for 3 days. A total therapeutic dose of 6–30 mg/kg/bw artesunate and 22.5–45 mg/kg/bw amodiaquine daily dose is recommended.

Available formulations: fixed-dose combination in tablets of 25 + 67.5 mg, 50 + 135 mg, or 100 + 270 mg of artesunate and amodiaquine respectively.

Adverse effects described: severe neutropenia, particularly in patients co-infected with HIV receiving antiretroviral therapy (zidovudine) and/or clotrimoxazole. Concomitant use of efavirenz increases exposure to amodiaquine and the risk of hepatotoxicity. These combinations should be avoided unless it is the only ACTs available.

#### *4.2.3 Artesunate + Mefloquine*

Doses of 4 mg/kg/bw per day of artesunate and 8.3 mg/kg/bw per day of mefloquine, once daily for 3 days.

A pediatric tablet formulation of 25 mg artesunate and 5.5 mg mefloquine hydrochloride (equivalent to 50 mg mefloquine base) and adult tablets with 100 mg artesunate and 220 mg mefloquine hydrochloride (equivalent to 200 mg mefloquine base) are available.

Mefloquine is associated with nausea, vomiting, dyskinesia, dysphoria and sleep disturbances, and has been well tolerated. Combination with rifampicin reduces its efficacy.

#### *4.2.4 Artesunate + Sulfadoxine-pyrimethamine*

Currently available in 50 mg artesunate tablets and fixed-dose combination tablets with 500 mg sulfadoxine +25 mg pyrimethamine; the dose is 4 mg/kg/bw per day of artesunate for 3 days and a single administration of 25/1.25 mg/kg/bw of sulfadoxinepyrimethamine, single dose on day 1 of treatment.

*Malaria-Transmission-Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.113746*

#### *4.2.5 Dihydroartemisinin + piperaquine*

With the use of this drug the cure rate is excellent (>95%), although in children under 5 years of age, the risk of therapeutic failure is increased by three times. The recommended doses are 4 mg/kg/bw per day of Dihydroartemisinin and 18 mg/kg/ bw per day of piperaquine, daily for 3 days for adults and children weighing ≥25 kg. Children weighing less than 25 kg should receive a minimum of 2.5 mg/kg/bw per day of Dihydroartemisinin, and 20 mg/kg/bw per day of piperaquine daily for 3 days. It is available as a fixed-dose combination in tablets of 40 mg Dihydroartemisinin and 320 mg piperaquine and pediatric tablets with 20 mg Dihydroartemisinin and 160 mg piperaquine.

There are factors that alter the efficacy of the drug and the response to therapy: the ingestion of high-fat meals modifies the absorption of piperaquine and increases the risk of arrhythmias, delayed ventricular repolarization with prolongation of the corrected QT interval in the electrocardiogram, and malnourished children are at high risk of not obtaining an adequate response [2, 29, 30].

#### **4.3 Treatment of uncomplicated malaria caused by** *P. vivax, P. ovale, P. malariae***, and** *P. knowlesi*

The goal of treatment of *P. vivax* malaria is twofold: to cure the acute infection in the blood and to clear the hypnozoites from the liver to prevent relapse.

In areas where *P. vivax* is sensitive to chloroquine, treatment of malaria with oral chloroquine at a dose of 25 mg/kg/bw is effective and well tolerated. It is started with a dose of 10 mg/kg/bw on the first day, continued on the second day with 10 mg/kg/ bw and it is ended on the third day with 5 mg/kg/bw.

ACTs are highly effective in the treatment of this parasitic species in areas where chloroquine-resistant *P. vivax* exists; ACTs containing piperaquine, mefloquine, lumefantrine are recommended.

In the therapy of uncomplicated *P. ovale, P. malariae*, and *P. knowlesi* malaria, the resistance of these species to these drugs has not been well characterized, and they are considered sensitive to chloroquine and should be treated with standard chloroquine or ACT regimens [2].

Tafenoquine: It is a new drug belonging to the family of 8-aminoquinoleins. It was discovered in 1978, in response to the search for a drug that acts on acute and latent forms of *P. vivax* infection and although the mechanism of action is not exactly known, it is hypothesized that it induces spontaneous oxidation by redox cycles, causing the death of the parasite. It has few adverse effects, and they occur in approximately 13%, predominantly gastrointestinal symptoms, vortex keratopathy without sequelae, prolongation of the QT interval, and hemolytic anemia in people with G6PD deficiency. In three studies subjected to meta-analysis, the efficacy of treatment with tafenoquine compared to primaquine was evaluated and showed no inferiority, being an alternative that improves treatment compliance and is administered in a single dose [31].

#### **4.4 Mixed malaria**

Common in endemic areas, ACTs are effective against all malaria species and are the shock treatment for mixed infections [2].

#### **4.5 Use of primaquine in the treatment of malaria**

To reduce the transmissibility of *P. falciparum* infection in areas of low transmission intensity, it should be administered in a single dose of 0.25 mg/kg/bw and accompanied by ACTs (except in pregnant women, children under 6 months of age, and women breastfeeding children under 6 months of age).

To prevent relapses in *P. vivax* malaria*, P. ovale* in children and adults (except pregnant women, children under 6 months, women breastfeeding children under 6 months, and persons with G6PD deficiency) should be treated with primaquine at doses of 0.25–0.50 mg/kg/bw, once daily for 14 days [2, 4].

#### **4.6 Treatment of severe malaria**

Treatment includes a general approach and the use of antimalarial drugs; general measures include: parenteral hydration, transfusion of globular or platelet concentrates; according to the patient's condition. In situations of advanced clinical deterioration, nutritional support, renal replacement therapy (hemodialysis), and mechanical ventilation may be required.

Severe malaria is a medical emergency, and it is essential to perform supportive measures and give full and effective parenteral or rectal doses of antimalarial drugs in the initial treatment. Two groups of drugs are available for intravenous administration: artemisinin derivatives (artesunate or artemether) and cinchona alkaloids (quinine and quinidine) [2, 4, 6, 32, 33].

The clinical and rapid assessment with emphasis on the patient's general condition includes: assessing the state of consciousness using the Glasgow scale, quantifying vital signs (blood pressure, frequency, and depth of respiration), as well as the degree of skin pallor.

General treatment for severe malaria and its complications:


Hydration: If there is no evidence of fluid overload, patients with oral intolerance (adults and pediatric) should receive 5% dextrose solutions, and those who tolerate the oral route, administer isotonic saline solution at a rate of 1–2 mL/kg/hour. Take care not to overhydrate the patient [2, 6].

Treatment of anemia: In adults, if the hematocrit <20 or Hb < 7 g/dL, transfuse whole blood or packed red cells over 6 hours [2, 6].

The advantages of artemisinin over quinine are evident, demonstrating a decrease in mortality with the administration of artesunate; it is simple and safe, it is applied in bolus intravenously or intramuscularly, without the adverse effects of quinine, nor the difficulties of intravenous dilution several times a day [2, 6, 32–34].

Antimalarial drugs: In any case of severe malaria, antimalarial chemotherapy should be initiated early [2, 4, 6, 35–40].

First line in severe malaria: The therapeutic scheme is of international use.

Artesunate: WHO (2012) has indicated that the isolated use of this parenteral drug is the initial treatment of choice for this clinical form, the benefit is due to the fact that rapid therapeutic plasma concentrations are obtained, it is well tolerated, unlike quinine it eliminates parasitemia faster and has few adverse effects, it can be administered intravenously or intramuscularly [40].

Dosage according to patient's weight:

a.Patient with less than 20 kg: 3 mg/kg/bw/dose.

b.Patient ≥20 kg: 2.4 mg/kg/bw/dose.

The first three doses of Artesunate are administered following an hourly interval; the first, upon admission (hour 0); the second 12 hours after the previous one and the third, 24 hours after the initial dose; with the option of prescribing additional doses, if the patient requires it. In this situation, continue with the medication until oral tolerance is recovered and a maximum of 7 days. Once the oral route is recovered, full therapy with Artemether 20 mg + Lumefantrine 120 mg for 3 days plus Primaquine at 0.50 mg/kg bw in a single dose is prescribed in case of *P. falciparum infection,* or in case of *P. vivax* or mixed infections at 0.25 mg/kg bw daily for 14 days.

Artemether attack dose: 3.2 mg/kg/bw and maintenance dose: 1.6 mg/kg/bw. First dose at admission (hour 0), then a maintenance dose every 24 hours until oral tolerance is achieved, for a maximum of 5 days. When tolerance is restored, oral treatment with Artemether 20 mg + Lumefantrine 120 mg for 3 days plus Primaquine at 0.50 mg/kg bw in a single dose in case of *P. falciparum infection*, or 0.25 mg/kg bw, daily for 14 days in case of *P. vivax* or mixed infections.

Quinine dihydrochloride dose of 10 mgs/kg/bw + Clindamycin 10 mgs/kg/bw, both intravenously. First dose at admission (hour 0), continue with Quinine every 8 hours plus Clindamycin every 12 hours until oral tolerance is recovered, for a maximum of 7 days. Depending on oral availability, complete 7 days with Quinine in tablets at 10 mg/kg bw every 8 hours, plus Clindamycin at 10 mg/kg bw every 12 hours for 7 days or Doxycycline at 4 mg/kg bw per day for 7 days, plus Primaquine at 0.50 mg/kg bw in single dose in case of *P. falciparum infection*, or 0.25 mg/kg bw per day for 14 days in case of *P. vivax* or mixed infection [2, 4, 34, 36–41].

Some authors propose giving high, supervised doses of Primaquine at 7 mgs/kg/ bw day for 14 days to reduce relapses of *P. vivax* and *P. falciparum* malaria [42–43].

#### **5. Conclusions**

In this chapter, the review of national and international literature related to malaria shows its importance worldwide as a potentially fatal disease, is transmissible in tropical countries, more frequent in Africa, Asia, Oceania, and Latin America; the alternative diagnostic methods are exposed with their strengths and weaknesses, especially the parasitological ones with the thick blood smear as the gold standard, accompanied by thin blood smear; also, the usefulness of RDTs in remote sites, where microscopy is not available for an immediate diagnosis. In relation to antimalarial treatment, the current guidelines and recommendations are presented with the use of Artemisinin combinations (ACTs) and their different presentations for the therapy of uncomplicated *P. falciparum* malaria, or in mixed malaria, and the conduct in case of severe malaria with the use of ACTs in their different forms of administration: oral, rectal, intramuscular, and intravenous. Finally, the indication of primaquine and tafenoquine to avoid relapses and contagion of this entity; without diagnostic delay and early initiation of medication to prevent fatal outcomes due to severe complications, we should be waiting for updates on the different diagnostic, therapeutic, and preventive options, as long as the fight toward the eradication of this disease is a reality in the world.

#### **Acknowledgements**

The author acknowledges to Dr. María Eugenia Guzmán Siritt, for her contributions to the review of the chapter.

#### **Conflict of interest**

"The author declares no conflict of interest".

*Malaria-Transmission-Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.113746*

#### **Author details**

Marisol Sandoval-De Mora Universidad de Oriente, School of Health Sciences "Dr Francisco Battistini Casalta", Ciudad Bolívar, Venezuela

\*Address all correspondence to: sandomarisol@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[22] De Monbrison F, Gérome P, Chaulet JF, Wallon M, Picot S, Peyron F. Comparative diagnostic performance of two commercial test for malaria in non-endemic area. European Journal of Clinical Microbiology & Infectious Diseases. 2004;**23**(10):784-786. DOI: 10.1007/s10096-004-1202-9

[23] Grobusch MP, Hanscheid T, Zoller T, Jelinet T, Buchard GD. Rapid immunochromatographic malarial antigen detection unreliable for detecting *Plasmodium malariae* and *Plasmodium ovale*. European Journal of Clinical Microbiology & Infectious Diseases. 2002;**21**:818-820. DOI: 10.1007/ s10096-002-0831-0

[24] World Health Organization 2017. False-negative RDT results and implications of the new report of histidine-rich protein 2/3 deletions of *P. falciparum*. World Health Organization. 2017. Available from: https://apps.who.

int/iris/handle/10665/ [Accessed: 28 May 2023]

[25] Voller A. The immunodiagnosis of malaria. In: Wernsdorfer WH, Mc Gregor I, editors. Malaria. Principles and Practice of Malariology. Edinburgh: Churchill Livingstone; 1988. pp. 815-827

[26] Farcas GA, Zhong KJ, Lovegrove FE, Graham CM, Kain KC. Evaluation of the Binax NOW ICT test versus polymerase reaction and microscopy for the detection of malaria in returned travelers. American Journal of Tropical Hygiene. 2003;**69**(6):589-592. DOI: 10.4269/ajtmh.2003.69.6.0690589

[27] WHO. WHO Evidence review group on malaria diagnosis in low transmission settings. Meeting report. Geneva: World Health Organization; 2012. Available from: https://www.cdn.who.int/media [Accessed: 29 May 2023]

[28] WHO. Malaria surveillance, monitoring and evaluation: a reference manual. Geneva: World Health Organization. Licence: CC BY-NC-SA 3.0 IGO. 2018. Available from: http://apps. who.int/iris [Accessed: 21 September 2023]

[29] Tarning J, Zongo I, Somé FA, Rouamba N, Parikh S, Rosenthal PJ, et al. Population pharmacokinetics and pharmacodynamics of piperaquine in children with uncomplicated falciparum malaria. Clinical Pharmacological Therapy. 2012;**91**(3):497-505. DOI: 10.1038/clpt.2011.254

[30] Global Antimalarial Resistance Network, (WWARN) DP Study Group. The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: A pooled analysis of individual patient data. PLoS Medicine. 2013;**10**(12):e1001564. DOI: 10.1371/

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[32] Padilla JC, Montoya R. Clinical care guidelines for malaria. Infection. 2011;**15**(4):302-323. DOI: 10.1016/ s0123-9392(11)70745-7

[33] Cuenca Abruch D, Gómez Johnson VH, Romo López A, Valente-Acosta B. Severe Plasmodium falciparum malaria. AnMed (Mex). 2018;**63**(2):134-137. Available from: www.medigraphic.com/analesmedicos [Accessed: 09 June 2023]

[34] MPPS. PAHO. Treatment guidelines in cases of Malaria. [Internet]. 1st edition. National Malaria Elimination Program. Caracas: Ministerio del Poder Popular para la Salud. 2017:1-118. Available from: https://iris.paho.org/bitstream/ handle/10665.2/34490/9789806678057\_ spa.pdf?sequence=1&is Allowed=y [Accessed: 29 May 2023]

[35] Albrecht-Schgoer K, Lackner P, Schmutzhard E, Baier G. Cerebral malaria: Current clinical and immunological aspects. Frontiers in Immunology. 2022;**13**:863568. DOI: 10.3389/fimmu.2022.863568

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*Malaria-Transmission-Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.113746*

[37] Esu E, Ea EE, Opie ON, Uwaoma A, Meremikwu MM. Artemether for severe malaria. Cochrane Database of Systematic Reviews. 2014;**2014**(9). CD010678. DOI: 10.1002/14651858. CD010678.pub2 [Accessed: 29 May 2023]

[38] WHO. Guidelines for the Treatment of Malaria. 2nd edition. Geneva: WHO Library Cataloguing-in-Publication Data; 2010. 1-542 pp. Available from: https://www.paho.org/en/node/50095 [Accessed: 30 May 2022]

[39] PAHO. Practical Manual for the Treatment of Severe Malaria. 3rd edition. World Health Organization. Geneva; 2012. 83 p. Available from: https://apps.who.int/iris/bitstream/ handle/10665/101443/9789243548524\_ spa.pdf;jsessionid=E48119EF1D80FF 4BC779A23B60DFE046?sequence=1 [Accessed: 07 July 2023]

[40] WHO. Management of severe malaria. Practical manual. 2012. Available from: http://www.mosquito. who.int /docs/hbsm\_toc.htlm [Accessed: 05 June 2023]

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[42] Poespoprodjo JR, Burdam FH, Candrawati F, Ley B, Meagher N, Kenangalem E, et al. Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: A cluster-randomised, controlled, open-label superiority trial. Lancet Infectious Disease 2022;**22**(3):367-376. DOI: 10.1016/S1473-3099(21)00358-3 [Accessed: 08 June 2023]

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et al. Higher-dose Primaquine to prevent relapse of *Plasmodium vivax* malaria. New England Journal of Medicine 2022;**386**(13):1244-1253. DOI: 10.1056/ NEJMoa2104226 [Accessed: 05 July 2023]

#### **Chapter 2**

## Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia

*Fitriani Kahar, Yuwono Setiadi, S.Y. Didik Widiyanto, Depri Ardiyansyah and Nurul Qomariyah*

#### **Abstract**

Malaria is a disease caused by Plasmodium and is characterized by recurrent fever, anemia, and hepatosplenomegaly. There are five species of Plasmodium that can infect humans. *P. falciparum* causes the most deaths, as do *P. vivax*, *P. ovale*, and *P. malariae* which usually cause mild malaria. The aim of this research is to determine the meaning, classification, epidemiology, symptoms, pathogenesis, diagnosis, mode of transmission, prevention, and treatment of malaria. Research method: This research is a descriptive observational study with a literature review design using databases from Google Scholar, accredited national journal Sinta, and reputable international journals such as Scopus, PubMed, Web of Science, and others. The research results show that malaria cases are still high in Indonesia every year. There are several risk factors for malaria such as attitude, behavior, environment, and physical environmental factors where you live, such as (temperature, humidity, livestock pens, houses without screen ventilation, stagnant water, or breeding places). Malaria treatment depends on several factors, including the type of Plasmodium that causes infection, the severity of the disease, and the disease the individual is suffering from. Prevention efforts need to be made by addressing various risk factors for malaria.

**Keywords:** malaria, transmission, diagnosis, prevention, Indonesia

#### **1. Introduction**

The disease caused by Plasmodium is malaria, which is characterized by recurrent fever, anemia, and hepatosplenomegaly. This disease varies from acute to chronic. During the acute phase, attacks of fever sometimes occur. During subsequent chronic stages, there are latent phases separated at relapse in recent times [1]. Malaria is also a health problem that causes death, especially in high-risk groups such as infants, pregnant women, children under five. Malaria also causes anemia and reduces work [2]. Malaria is an endemic disease in Indonesia and affects all components of the blood. The most common complications are anemia and thrombocytopenia. This is a concern of the scientific literature because it is associated with mortality [3]. Indonesia

is a tropical country so that malaria is an infectious disease, especially in some areas which are said to be endemic, especially outside Java, such as Jayapura and others [4].

The type of Plasmodium that causes the infection determines the intensity of the symptoms of malaria. Four species of Plasmodium are known: *Plasmodium vivax*, is one of the most common infections causing vuvax or tertian malaria or vivax; *Plasmodium falciparum*, which causes tropical malaria or falciparum malaria, and causes malaria quartana or malriae, nephrotic syndrome and plasmodium ovale which are found in the West Pacific and Africa, resulting in milder outbreaks and frequent outbreaks [5]. There are other species that also cause malaria, that is *Plasmodium knowlesi* [6]. In severe cases will occur malaria cerebral which also has a fatal impact. Nationally, cases have decreased but are still frequently found throughout Indonesia. This disease requires expertise from an appropriate clinical perspective in determining the diagnosis and therapy in patients. Currently, the management of cerebral malaria in Indonesia is guided by the 2017 Malaria Case Management Book [5].

In many countries around the world, malaria is still a public health problem. Even though the Malaria Implementation and Eradication Program has been started since 1959, the mortality and morbidity rates are still high in this country of Indonesia. Every year, 300 million people are attacked and 2–4 million die. Therefore, the Ministry of Health assesses malaria as a very important problem [1].

In 2010 in Indonesia there were 65% of endemic districts where only about 45% of the population in these districts was at risk of contracting malaria. Based on the results of a community survey during 2007–2010, the prevalence of malaria in Indonesia decreased from 1.39% (Riskesdas 2007) to 0.6% (Riskesdas 2010). Meanwhile, based on reports received during 2000–2009, the malaria morbidity rate tended to decrease, namely 3.62 per 1000 population in 2000 to 1.85 per 1000 population in 2009 and 1.96 in 2010. Meanwhile, the death rate due to malaria reached 1.3% [2, 7].

The national prevalence of malaria based on the 2010 Riskesdas results was 0.6% where provinces with API above the national average were West Nusa Tenggara, Maluku, North Maluku, Central Kalimantan, Bangka Belitung, Riau Islands, Bengkulu, Jambi, Central Sulawesi, Gorontalo and Aceh. The highest prevalence rates were found in eastern Indonesia, namely in West Papua (10.6%), Papua (10.1%) and East Nusa Tenggara (4.4%) [2].

Symptoms that patients show upon their arrival at Manado Central Hospital (now known as Bethesda Omolon Hospital and Prof.dr. R.D.Kandou Hospital. In 1993, malaria cases at Bethesda Tomohon Hospital showed objective symptoms of icterus 3.0%, hepatomegaly 43%, splenomegaly 40.7%, and pallor 6.6%.Other common symptoms are vomiting 31–37%, dizziness 75–82%, nausea 74–76%, chills 64–82%, and fever 92–96% [1].

In North Sulawesi, Indonesia, especially in North Sulawesi Hospitals and Health Centers, malaria itself is a disease that is often found. Malaria infection accounts for 9% of hospitalizations, there are 400 cases of mild malaria and 30–40 cases of severe malaria each year, and 6–7 of them die every year. There is a mortality rate from malaria reaching 15.7% in the most common problems that arise are jaundice and kidney failure in Manado City [1].

In South Jayapura District, Indonesia, it is an endemic area with the third highest malaria rate of the 5 districts in Jayapura city. Malaria cases in Jayapura City in 2019 were 28,648 cases with an API of 92.55/1000 population, in 2020 there were 28,075 cases with an API of 89.35/1000 population, while in 2021 there were 30,235 cases with an API of 99.49/1000 population [8].

#### *Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

However, equipment and human resources still greatly influence how quickly and precisely treatment is provided in city and district hospitals. As of December 2009, only a few hospitals, mainly in Manado and Minahasa, had data on malaria patients [1].

#### 1.Problem Formulation


#### 2.Objective


It is hoped that writing this paper will be useful for readers, especially for people in endemic areas to prevent malaria from occurring. Become a source of scientific literature related to malaria.

#### **2. Methodology**

Research method: This research is a descriptive observational study with a literature review design with databases from Google Scholar, Sinta accredited national journals, and reputable international journals such as Scopus, Pubmed, Web of Science and others.

#### **3. Result and discussion**

#### **3.1 Definition of malaria**

Malaria is an infectious disease caused by the bite of the Anopheles mosquito and Plasmodium parasites. Headache, vomiting, chills, fever, and pain in joints and muscles are symptoms of malaria. If treated properly, certain drugs can cure malaria [9]. Malaria is a disease that attacks humans, birds, monkeys and other primates, reptiles and rodents caused by infection with protozoa of the genus Plasmodium. The incidence or transmission of infectious diseases is determined by risk factors/determinants called host, agent and environment [10].

The main cause of this disease is the female Anopheles mosquito which spreads the infection by biting. Anopheles mosquito bites contain parasites in their saliva which enter the blood of the humans they bite. Parasites migrate to the liver, where they mature and reproduce. There are five species of Plasmodium that infect and can infect humans. *P. falciparum* causes the most deaths, as do *P. vivax*, *P. ovale* and *P. malaria* usually cause milder forms of malaria. *P. knowlesi* rarely causes disease in humans. A rapid antigen-based test or a microscopic blood test of a blood sample is usually used to diagnose malaria. Due to cost and complexity, methods for detecting parasite DNA using polymerase chain reactions have not been widely used in areas where malaria is common [9].

#### **3.2 Epidemiology of malaria**

Even though there has been a reduction in Annual Parasite Incidence (API) nationally, in areas with high malaria cases the API rate is still very high compared to the national rate, whereas in areas with low malaria cases extraordinary events (KLB) often occur as a result of imported cases. In 2011 the number of reported malaria deaths was 388 case [2].

#### *Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

Information from the World Health Organization (World Health Organization) in 2013 reported that there were 197 million cases of malaria with 548,000 deaths, and 78% of these cases included child deaths under the age of 5 [11]. Furthermore, according to WHO, there were 198 million cases of malaria worldwide in 2014, namely 584. Malaria is widespread in many places around the world, especially in tropical and subtropical regions such as Indonesia. In Indonesia, about 35 percent of the population lives in malaria-prone areas. 584,000 deaths from severe malaria each year. Malaria epidemics occur almost every year in several endemic areas in Indonesia [4]. Areas such as East Nusa Tenggara, West Nusa Tenggara, Maluku, North Maluku, Central Kalimantan, Bangka-Belitung, Riau Islands and Bengkulu are included in the malaria red zone. Next are Jambi, Central Sulawesi, West Sulawesi, Gorontalo and Aceh [4].

Research results related to the prevalence of malaria show that Malaria sufferers were more at the age of 24–35 years, namely as many as 264 sufferers (41.1%), malaria sufferers were more in the female sex as many as 323 people (50.3%), malaria sufferers were more in patients who worked as private employees, namely 410 people (63.9%). More malaria sufferers were found living in urban areas, namely 447 sufferers (69.6%) [12].

Here are some common approaches to treating malaria: Malaria is a disease that is naturally transmitted by pathogens (Plasmodium spp.), definitive hosts (Anopheles spp. and intermediate hosts (humans) [4].

The epidemiological components of malaria consist of: the first pathogen, Plasmodium spp. parasites. Parasites that live in the human body reproduce by consuming red blood cells (RBC), causing anemia in the infected or the host. Second, there are two types of hosts: Humans as intermediate hosts (temporary, because sexual reproduction does not occur) and mosquitoes as definitive hosts (permanent, because sexual reproduction does not occur). Anopheles spp. is a species of mosquito that transmits malaria. However, not all species causes malaria. Plasmodium is spread by malaria, which is bitten by a mosquito (carrier) and then enters the carrier's body via blood cells in various asexual stages. Endemic malaria [4].

#### **3.3 Classification of malaria**

Malaria is an infectious disease caused by Plasmodium parasites which can be characterized by fever, hepatosplenomegaly, and anemia. Plasmodium lives and reproduces in human red blood cells. This disease is naturally transmitted through the bite of a female Anopheles mosquito.

Plasmodium species in humans are:

a.*Plasmodium falciparum* (*P. falciparum*).

b.*Plasmodium vivax* (*P. vivax*)

c.*Plasmodium ovale* (*P. ovale*)

d.*Plasmodium malariae* (*P. malariae*)

e.*Plasmodium knowlesi* (*P. knowlesi*)

The most common types of Plasmodium found in Indonesia are *P. falciparum* and *P. vivax*, while *P. malariae* can be found in several provinces, including Lampung, East Nusa Tenggara, and Papua. P ovale has been found in East Nusa Tenggara and Papua. In 2010 on the island of Borneo it was reported that *P. knowlesi* could infect humans where previously it only infected primates/monkeys and until now [2].

According to Harijanto [13], Malaria is further divided according to its Plasmodium type, including:

#### *3.3.1 Plasmodium falciparum (tropical malaria)*

Tropical malaria, also known as tropical falciparum malaria, is the most severe form of malaria. This disease is characterized by anemia, fever, blood parasites, and splenomegaly, often causing complications. The disease lasts 9–14 days. Tropical malaria affects all types of red blood cells caused by *Plasmodium falciparum*. The only Plasmodium species with duplicated nuclear chromatin in the form of a ring or small rings one-third the diameter of a normal red cell. Spread of tropical malaria is classified when *Plasmodium falciparum* infects red cells for life, often resulting in the formation of blood cell parasites that produce multiple protrusions that can adhere to the endothelial lining of capillary walls due to thrombotic occlusion and local ischemia. This infection is more serious than other infections and causes many complications such as cerebral malaria, gastrointestinal disorders and black hemorrhagic fever.

#### *3.3.2 Plasmodium malariae (Kwartama malaria)*

Tropozoites of *Plasmodium malariae* which are smaller than *Plasmodium vivax* have more compact or bluer cytoplasm. Mature trophozoites have dark brown to black grains and are often grouped in groups.

#### *3.3.3 Plasmodium ovale (malaria ovale)*

Malaria ovale, known as *Plasmodium ovale*, is similar in shape to *Plasmodium malariae*, but the schizont consists of only eight merozoites and has a black mass in the center. Red blood cells infected with *Plasmodium ovale* are usually oval or irregular in shape with a visible ciliated pattern. Of all the types of malaria caused by *Plasmodium ovale*, malaria ovale is the mildest. The incubation period varies from 11 to 16 days, but the latent period can be up to 4 years. Attacks last 3 to 4 days without treatment, rarely more than 10 days, and occur at night.

#### *3.3.4 Plasmodium vivax (tertian malaria)*

*Plasmodium vivax* infection, or tertian malaria, can sometimes affect the young red blood cells, which are larger than normal red blood cells. It resembles *Plasmodium falciparum* in appearance, but vivax trophozoites become amoebae with age. Consists of 12–24 oval merozoites with yellow pigment at the poles. Oval gametocytes occupy almost all of the red blood cells, eccentric chromatin and yellow pigment. Symptoms of this type of malaria last 48 hours as shown in the malaria triad, causing intermittent fever every 4 days, with a peak of fever occurring every 72 hours. Of all the Plasmodium and malaria species that invade the body, tropical malaria is the most important. It is manifested by unstable fever, anemia, splenomegaly, multiple parasites and frequent complications [13].

*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

#### **3.4 Scope malaria**

Malaria is a disease in the world, especially in tropical and subtropical regions, the cause of which is the Plasmodium parasite, which is transmitted through the bite of the Anopheles mosquito [14].

The scope of malaria covers several important aspects, including:


#### **3.5 Symptoms of malaria**

Manifestations of malaria are fever, anemia and enlargement of the spleen [16]. In people who have been taking antimalarial drugs for prevention, symptoms of malaria may appear later, usually 8 to 25 days after infection. In all types of malaria, the illness is generally flu-like and can mimic sepsis, gastroenteritis, and viruses. Symptoms include: Headache, fever and chills, arthralgia, vomiting, hemolytic anemia, jaundice, urinary hemoglobin, retinal damage and seizures. The main symptoms of malaria are paroxysmal symptoms, including cyclic fever and persistent chills. Then infection with *P. vivax* and *P. ovale* on the second day, called tertiary fever, and every third day, called quarantine fever, with *P. falciparum* can cause recurring fever every 36 to 48 hours or less. One, almost constant fever. *Plasmodium falciparum*, commonly called falciparum malaria, is the main cause of severe malaria. Symptoms of falciparum malaria appear 9 to 30 days after infection. Neurologic symptoms such as nystagmus, postural disturbances, opisthotonos, seizures or coma are common in individuals with cerebral malaria [17].

#### **3.6 Risk factors of malaria**

#### *3.6.1 Characteristics of the physical environment*

Based on the results of the research that has been carried out, factors that can occur are caused by the roof/wall of the house that is not tightly closed due to the type of wall made of boards or plywood, there is no ceiling, the ventilation of the house does not use gauze, there is a pool of water or *breeding place* such as (gutters, ponds and swamps) as well as houses close to *resting place* or bushes. The factors that have been described will result in the presence of Anopheles sp. mosquitoes if not immediately addressed and corrected.

#### *3.6.2 Behavioral characteristics*

Lack of public knowledge about the importance of preventing malaria in their environment and lack of support for malaria cases. It can be concluded that the factors that cause malaria are related to the individual's lack of concern for the environment around his home. Physical environment variables such as the density of the walls of the house, the screens on the ventilation, and the ceilings of the house have relationship with malaria incidence. In addition, behavioral variables such as actions also play a role in the spread of the disease.

To reduce the risk of malaria, people are expected to keep their homes free of mosquitoes by installing tight walls, ceilings and screens for ventilation. In addition, they expect more attention to the environment around the house by adopting environmental management practices, that is, H. save, empty, clean and empty clogged drains and trim bushes.

Malaria control efforts involve environmental management, prevention of mosquito bites, treatment of infected cases, as well as education and community participation. This aims to reduce the presence of mosquito vectors and stop the Plasmodium transmission cycle in the human population [8].

#### **3.7 Pathogenesis of malaria**

The rupture of the blood schizont is caused by the release of several antigens and can cause fever in the body. Macrophage cells, monocytes and lymphocytes can be

#### *Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

stimulated by antigens to release cytokine types including Tumor Necrosis Factor. And IL-6 V then enters the hypothalamus, the body's temperature control center. In the four plasmodia it takes a different time for sizogony [2, 18].

Excessive destruction of red blood cells in the malaria parasite is the cause of decreased hemoglobin values, and anemia also occurs due to disturbances in the spinal cord in forming red blood cell [19]. As a result of hemolysis, there is sequestration of erythrocytes in the spleen and other organs, and depression in the bone marrow [16]. In severe cases, cerebral malaria will occur in a febrile patient with decreased consciousness [5]. Cerebral malaria is an acute encephalopathy that meets three criteria, namely coma that cannot be awakened, or coma that persists for >30 minutes after the seizure and is accompanied by *P. falciparum* indicated by a blood smear [20].

Infected or uninfected red blood cells are damaged, causing anemia. Plasmodium ovale and *Plasmodium vivax* infect immature erythrocytes, making up 2% of total erythrocytes, and *P. malariae* only infects mature erythrocytes, making up 1% of total erythrocytes. All types of red blood cells are infected with *Plasmodium falciparum*, so anemia can occur in both acute and chronic infections. Plasmodium lesions are caused by splenic macrophages and lymphocytes, which are reticular endothelial cells. These inflammatory cells enlarge the spleen. Malignant malaria caused by *P. falciparum* has a unique pathogenesis. Once infected with *P. falciparum*, the parasite's red blood cells spread through the capillaries of the body's organs. In addition, the bumps that form on the surface of infected red blood cells contain various *P. falciparum* antigens. Cytokines such as TNF and IL-6, produced by macrophages, monocytes and lymphocytes, activate capillary endothelial cell receptor expression. Cell adhesion occurs when nodules attach to endothelial cell receptors in capillaries. This process causes tissue ischemia due to capillary occlusion. The "asterisk" method - clustering - also supports this inhibition (**Figure 1**) [22].

**Figure 1.** *Plasmodium life cycle in general [21].*

#### **3.8 Immune response against malaria**

The immune response to malaria infection involves a number of complex mechanisms. When the malaria parasite (Plasmodium) enters the human body through the bite of a vector mosquito, the body's immune system will respond to fight the infection. Following are some of the important stages in the immune response to malaria:


It is important to note that Plasmodium has the ability to evade or trick the human immune system by changing their protein surface on a regular basis. This allows them to evade detection by the immune system and makes it difficult to develop an effective immune response.

The immune response to malaria can be complex and varies depending on the type of parasite, individual immunity, and other factors. Because of this complexity the development of an effective vaccine for malaria has become a significant challenge in the management of this disease. However, research and efforts are continuing to understand the mechanisms of the immune response and develop effective vaccination strategies [15, 23].

#### **3.9 Diagnosis of malaria**

In areas where malaria is rare, the diagnosis of malaria requires a high degree of suspicion, which can be triggered by:


*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*


Blood smear microscopy or rapid antigen-based test (RDT) is often used to confirm the diagnosis of malaria. In 2010, approximately 165 million meninges were tested for malaria, and microscopy is the most commonly used method of identifying malaria parasites. Despite its widespread use, microscopy has two major drawbacks [2].

In border areas, many testing facilities are not well equipped and the accuracy of results depends on the performance of blood membrane testing kits and the number of parasites in the blood. The sensitivity of blood samples varies between 75 and 90°, up to 50% under optimal conditions. Commercially available RDTs are often more accurate than blood films in predicting the presence of malaria parasites, but their diagnostic sensitivity and specificity vary widely between manufacturers and cannot be determined. Any healthy person who has traveled to a malaria endemic area should be suspected of having malaria and examined where tests are available. In places where laboratory diagnostic tests cannot be performed, the use of pre-existing fever as an indication for treatment of malaria has become widespread. As a result, the popular notion that "fever is synonymous with malaria if proven otherwise" has spread. Malaria over diagnosis and poor non-malarial therapy limit this approach, consume limited resources, reduce trust in the health system and increase drug resistance. Although assays that rely on polymerase chain reaction have been developed, their complexity has prevented their widespread use in areas where malaria is common. Increased resistance to polymerase chains has been developed, but because of its complexity it is not widespread in areas where malaria is common [2].

#### **3.10 Transmission of malaria**

The determinants of malaria transmission are divided into two broad categories. First, the factors that have a direct effect, the average mosquito bites humans in a day, the average Plasmodium gametocytes in the population, the length of the sporogonic cycle in the mosquito's body, the average daily survival rate of mosquitoes. Second, indirect factors, including environment and climate, rainfall, drought, management of the artificial environment, changes in vector biting patterns, air temperature, humidity, importation of malaria parasites through population movements and migration of non-immune populations [24].

One of the ways that malaria can be transmitted is by the bite of a vector mosquito infected with Plasmodium. Here are some ways of transmitting malaria:

1.Anopheles mosquito bites: The main cause of malaria is the bite of the Anopheles mosquito. When a mosquito bites a person infected with malaria, Plasmodium in their blood can enter the mosquito's body. When the mosquito bites another person, Plasmodium infects the person bitten and causes a malaria infection.


#### **3.11 Prevention of malaria**

Efforts to eradicate malaria in Indonesia have not achieved optimal results due to several factors such as the prevalence of malaria mosquitoes, the high number of cases, human resources, costs and infrastructure. Therefore, the best course of action is to prevent and stop the spread of the parasite. Many efforts can be made to prevent and eradicate the spread of malaria parasite [25].

Methods for preventing mosquito bites are particularly important in high prevalence areas. It is recommended to wear long sleeves and long pants when going out, especially at night, in rural or suburban areas with lots of rice fields, swamps or fish ponds (ideal breeding grounds for malaria-carrying mosquitoes).

Efforts to reduce morbidity and mortality are carried out through a malaria eradication program whose activities include early diagnosis, prompt and appropriate treatment, and vector surveillance and control in terms of public education and understanding of environmental health, all of which are aimed at breaking the chain of malaria transmission.

Resistance cases of malaria parasites to chloroquine were first discovered in East Kalimantan in 1973 for *P. falciparum*, and in 1991 for *P. vivax* in Nias. Since 1990, cases of resistance have been reported to have spread in all provinces in Indonesia. In addition, there have also been reports of resistance to Sulfadoxine-pyrimethamine (SP) in several places in Indonesia. This situation can increase the morbidity and mortality of malaria. Therefore, to overcome this problem of resistance (multiple drug resistance) and the existence of new anti-malarial drugs that are more patent, the government has recommended drugs of choice to replace chloroquine and SP, namely a combination of artemisinin derivatives with other anti-malarial drugs which are commonly referred to as Artemisinin based [2].

#### **3.12 Treatment of malaria**

Treatment of malaria depends on several factors, including the type of Plasmodium causing the infection, the severity of the disease, and the individual's health condition [9].

1.Antimalarial drugs: Antimalarial drug therapy is the main step in the treatment of malaria. Several types of drugs are used including:

*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*


It is important to note that antimalarial drug resistance is becoming an increasingly serious problem in some areas. Therefore, it is important to follow medication recommendations and consult a doctor who is experienced in treating malaria. In addition to treatment, prevention of malaria is essential, including the use of insecticide-treated nets and the prophylactic use of antimalarial drugs for those living in or traveling to remote areas. Use of mosquito repellents and control of mosquito vectors through eradication programs or the use of chemical insecticides (**Table 1**) [9].

#### **4. Conclusions**

Tackling the malaria problem requires a comprehensive approach that includes vector prevention, effective treatment, access to diagnosis and treatment, and research to develop more effective vaccines. Global efforts such as vector control campaigns, distribution of insecticide-treated bed nets and vaccination initiatives have helped reduce the global burden of malaria.

There are several risk factors for the occurrence of malaria such as attitudes, behavior, environment and physical environmental factors of residence such as (temperature, humidity, presence of cattle pens, the house is not ventilated through gauze, there are stagnant water or breeding grounds. Treatment of Malaria Treatment of malaria depends on several factors, including the type of Plasmodium that causes the infection, the severity of the disease and the individual's illness. It is necessary to carry out prevention efforts by addressing various risk factors for malaria to prevent cases of malaria. One way to prevent and overcome malaria is to improve individual and environmental sanitation.

**No Researcher Research title Results Discussion** 1 Ragil Setiabudi, [27] Systematic Review: Risk of Malaria as an Infectious Disease in Indonesia Based on the similarity of variables between researchers, there are 21 significant risk factors statistically, namely the presence of mosquito breeding places, without screens/barriers on ventilation of the house, not using mosquito coils, presence of bushes, presence of puddles water, presence of paddy fields, presence of ditches/gutches, presence of animal cages, poor housekeeping, house walls not tight, no ceiling, construction of non-permanent house floors, frequent activities outside the home at night, not using mosquito nets when sleeping, hanging clothes in the house, not using pesticides/insecticides, not using mosquito repellant/topical repellant, low education, income below the minimum wage, non-compliance with taking medication, malnutrition status with an average OR = 5.30. Minimum value OR = 0.26 and maximum value OR = 16.92. There are only two protective factors, namely frequent using mosquito nets on the bed (OR = 0.26) and having a ceiling (OR = 0.69).Risk factors for malaria incidence in Indonesia which means statistically there are 21 namely the presence of mosquito breeding places, without gauze/barrier on ventilation house, do not use mosquito coils, the presence of bushes, the presence of standing water, there are rice fields, there are ditches/ditches, existence of animal cages, cleanliness bad house, the walls of the house are not tight, no ceiling house, construction house floors are not permanent, often outdoor activities at night did not use mosquito nets at the time sleep, hang clothes inside house, do not use pesticides/insecticides, do not use repellant/repellent topical medication mosquitoes, primary education, income in below the minimum wage, non-compliance taking medication, poor nutritional status. The average OR for the incidence of Malaria is 5.30 The protective factor for the occurrence of Malaria is

the frequent use of mosquito nets on the bed and the

presence of a ceiling


mosquitoes spread.

*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

2


*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*


**Table 1.** *Table of literature research results.*

Manifestations of malaria are fever, anemia and

spleen enlargement.

The life cycle of the parasite takes place in humans

and in mosquitoes.

*Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia DOI: http://dx.doi.org/10.5772/intechopen.112982*

#### **Acknowledgements**

Thank you to the Poltekkes Kemenkes Semarang who have contributed invaluable in writing this scientific paper, and to the team that has assisted in collecting data in this study.

#### **Funding**

Nil.

#### **Conflict of interest**

No conflicts of interest are disclosed by the authors.

#### **Notes/thanks/other declarations**

The concept of this paper was developed by F.K, Y.S, S.Y.D.W, D.A, and NQ, who also wrote the script. The final manuscript submitted has been read and approved by all authors.

#### **Author details**

Fitriani Kahar1 \*, Yuwono Setiadi<sup>2</sup> , S.Y. Didik Widiyanto1 , Depri Ardiyansyah3 and Nurul Qomariyah1

1 Department of Health Analyst, Ministry of Health Polytechnic, Semarang, Indonesia

2 Department of Nutrition, Ministry of Health Polytechnic Semarang, Indonesia

3 Department of Environmental Health, Health Polytechnic Ministry of Health, Semarang, Indonesia

\*Address all correspondence to: fitrianikahar555@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 2
